We propose to investigate whether the increased susceptibility of cortisol-induced cleft palate in the sensitive AJ mouse strain as compared to the insensitive CBA and C57BL strains may be due to higher levels of cytosol receptors for cortisol in AJ palatal anlagen. We hytothesize that the mechanism by which corticoids induce cleft palate is the same as that by which corticoids produce their physiologic effects in other tissues, namely, binding of corticoid to a cytosol receptor, uptake by nuclei, and activation or depression of transcription and translation. Since other cleft palate-inducing teratogens are more effective in the sensitive AJ strain, we plan to determine whether AJ palates also have higher levels of these or other receptor which bind to other cleft-palate teratogens. It will also be determined whether cortexolone, a corticoid effects in vitro by competing with corticoids for their receptors, can prevent the production of cleft palate by corticoids in mice in vivo. Corticoid and other cleft palate teratogen receptors will also be sought in skin fibroblast cultures of infants with and without cleft palate in the hope that receptor level determinations in amniotic cells may establish the screen for cleft palate susceptibility after maternal exposure to potential cleft palate teratogens. In short, we hope to delineate the molecular chain of events involved in the action of a teratogen in both animals and humans with cleft palate and lip as a model of drug-induced teratogenesis.